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A high-throughput label-free nanoparticle analyser

Abstract

Synthetic nanoparticles and genetically modified viruses are used in a range of applications, but high-throughput analytical tools for the physical characterization of these objects are needed. Here we present a microfluidic analyser that detects individual nanoparticles and characterizes complex, unlabelled nanoparticle suspensions. We demonstrate the detection, concentration analysis and sizing of individual synthetic nanoparticles in a multicomponent mixture with sufficient throughput to analyse 500,000 particles per second. We also report the rapid size and titre analysis of unlabelled bacteriophage T7 in both salt solution and mouse blood plasma, using just 1 × 10−6 l of analyte. Unexpectedly, in the native blood plasma we discover a large background of naturally occurring nanoparticles with a power-law size distribution. The high-throughput detection capability, scalable fabrication and simple electronics of this instrument make it well suited for diverse applications.

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Figure 1: Device schematics and detector response.
Figure 2: Controlling particle flow.
Figure 3: Detection bandwidth.
Figure 4: Analysis of a polydisperse nanoparticle mixture.
Figure 5: Size and concentration measurements of unlabelled bacteriophage T7 in salt solution.
Figure 6: Particle size distribution and T7 phage detection in mouse blood.

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Acknowledgements

This research was supported by a National Institutes of Health Program of Excellence in Nanotechnology grant (U01-HL080718). The authors thank C. Axline for construction of the pressure manifold used to control flow in the microfluidic system, and G. Braun for valuable discussions. The authors also acknowledge use of the UC Santa Barbara Nanofabrication Facility, a part of the NSF-supported National Nanofabrication Infrastructure Network (NNIN).

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Contributions

J.-L.F. fabricated the analyser, performed the experiments and analysed the data. J.-L.F. and A.N.C designed the analyser. J.-L.F., T.T. and A.N.C. designed the experiments with contributions from E.R. J.-L.F. and A.N.C. wrote the manuscript with contributions from T.T. T.T. performed the biological procedures, including phage synthesis. C.M.M. contributed to the fabrication of the fluidic mold.

Corresponding author

Correspondence to Andrew N. Cleland.

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The authors declare no competing financial interests.

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Fraikin, JL., Teesalu, T., McKenney, C. et al. A high-throughput label-free nanoparticle analyser. Nature Nanotech 6, 308–313 (2011). https://doi.org/10.1038/nnano.2011.24

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